Patient-reported outcomes following free flap lower extremity reconstruction: A systematic review and meta-analysis.

PURPOSE: Free flap reconstruction in the lower extremity has shown success for the management of large and complex defects, restoration of function, and favorable aesthetic outcomes. Patient-reported outcomes (PROs) have not been well explored in previous literature. This meta-analysis aimed to provide a comprehensive summary of PROs after free flap reconstruction in the lower extremity. METHODS: We searched MEDLINE and Embase from 1946 to 2021 for studies reporting on PROs following free flap reconstruction in the lower extremity. RESULTS: Overall, 53 studies were included, and 11 studies reported validated PRO measures for meta-analysis. A total of 1953 patients underwent reconstruction with 1958 free flaps for lower limb defects with a mean follow-up of 3.26 (0.25-7.83) months. The mean postoperative Lower Extremity Functional Scale (LEFS) scores were 60.3 (±12) out of 80 points (4 studies, 85 patients). The mean postoperative AOFAS scores were 75.1 (±15) out of 100 points (4 studies, 68 patients). The mean postoperative SF-36 scores were 88.1 (±8.0) out of 100 points; mental health component was 48.7 (±8.9), and physical component was 38.4 (±8.2), out of 50 points (4 studies, 88 patients). CONCLUSION: Our findings demonstrated that patients report improved physical health, mental health, and function following lower extremity reconstruction with free flaps. Patients reported similar improvements in functional scores following lower extremity reconstruction regardless of their free flap type. Furthermore, patients with myocutaneous flaps may have improved mental health and worse physical health scores when compared to perforator flaps. The evidence profiles presented in this review indicate that additional research is needed to help guide future decision-making.

Outcomes of Immediate Breast Reconstruction in Triple Negative Breast Cancer: A Propensity Score-Matched Analysis.

PURPOSE: Triple negative breast cancer (TNBC) patients have a significantly worse prognosis and survival compared to non-TNBC patients. Mastectomy and immediate breast reconstruction (MIBR) is associated with higher rates of complications overall, but whether MIBR significantly increases oncological risk in TNBC patients has not been fully elucidated. Our study aimed to evaluate the oncological safety of MIBR in patients with TNBC compared to non-TNBC. METHODS: A 6-year prospectively maintained retrospective database at The Ottawa Hospital was reviewed from January 1, 2013 to May 31, 2019. Propensity score-matching was performed using the nearest-neighbour method with a matching ratio of 2:1. Kaplan-Meier and log rank tests were performed to provide statistical comparison of disease-free interval (DFI). DFI was defined as time from MIBR to locoregional recurrence or disease-specific mortality. P-value < 0.05 indicated statistical significance. RESULTS: Of 277 eligible patients, 153 patients were matched. The cohort consisted of 51(33%) TNBC patients and 102 (67%) non-TNBC patients after 2:1 propensity score-matching. The rates of delays to first radiochemotherapy [17 (33%) vs.14 (14%), p = 0.10], postoperative complications [13 (26%) vs. 34 (33%), p = 0.50], and locoregional recurrence [2 (1.96%) vs. 1 (1.96%), p = 1.0] were statistically similar in TNBC and non-TNBC, respectively. DFI was not significantly different in TNBC compared to non-TNBC patients (log-rank p = 1.0). There was no mortality in this cohort. CONCLUSIONS: This 6-year retrospective 2:1 propensity score-matched cohort study demonstrated similar oncological safety for MIBR in patients with TNBC and non-TNBC. Overall, these findings provide additional support for the oncological safety of MIBR in TNBC. Therefore, MIBR remains a therapeutic option for patients with TNBC.

The Effect of Neoadjuvant Chemotherapy on Safety Outcomes Following Immediate Breast Reconstruction.

BACKGROUND: Mastectomy and immediate breast reconstruction (MIBR) are becoming an increasingly popular option for women with breast cancer. However, MIBR is associated with a higher risk of postoperative complications compared to mastectomy alone, which may delay adjuvant cancer therapy. The main objective of this retrospective cohort study was to investigate oncologic outcomes in MIBR patients with and without neoadjuvant chemotherapy (NACT). METHODS: A 6-year retrospective study of breast cancer patients treated with MIBR was conducted from January 2013 to May 2019. The primary outcome was a delay in adjuvant radiochemotherapy. Secondary outcomes included postoperative complications and locoregional recurrences. RESULTS: Of 1832 patients reviewed, 300 (7.1%) were included. The cohort consisted of 277 (92%) MIBR patients without NACT and 23 (7.7%) with NACT. There was significantly more N1 and N2 tumor node status in the non-NACT group compared to the NACT group (p<0.001). The overall complication rates were similar in the NACT group compared to non-NACT (37.5% versus 21.7%, p=0.148). The rates of major and minor complications were also similar between NACT and non-NACT groups (Major: 29.6% versus 21.7%, p=0.823) and (Minor: 26.7% versus 8.70%, p =0.0970). The rates of locoregional recurrence (p=1.00), time to adjuvant therapy (p=0.629), and rates of delay (p=0.305) was also similar between groups. Overall survival was significantly lower in the NACT group compared to non-NACT (98.2% versus 82.6%, p<0.001). CONCLUSIONS: There was no difference in complication rates, or timing to adjuvant therapy, among MIBR patients with and without NACT. However, MIBR patients who received NACT had worse overall survival than MIBR patients without NACT.

Early oral intake and early removal of nasogastric tube post-esophagectomy: A systematic review and meta-analysis.

BACKGROUND: Early oral intake (EOI: initiated within 1 day) and early nasogastric tube removal (ENR: removed ≤2 days) post-esophagectomy is controversial and subject to significant variation. AIM: Our aim is to provide the most up-to-date evidence from published randomized controlled trials (RCTs) addressing both topics. METHODS: We searched MEDLINE and Embase (1946-06/2019) for RCTs that investigated the effect of EOI and/or ENR post-esophagectomy with gastric conduit for reconstruction. Our main outcomes of interest were anastomotic leak, aspiration pneumonia, mortality, and length of hospital stay (LOS). Pooled mean differences (MD) and risk ratios (RR) estimates were obtained using a DerSimonian random effects model. RESULTS: Two reviewers screened 613 abstracts and identified 6 RCTs eligible for inclusion; 2 regarding EOI and 4 for ENR. For EOI (2 studies, n = 389), was not associated with differences in risk of: anastomotic leak (RR: 1.01; 95% CI: 0.407, 2.500; I2 : 0%), aspiration pneumonia (RR: 1.018; 95% CI: 0.407, 2.500), mortality (RR: 1.00; 95% CI: 0.020, 50.0). The LOS was significantly shorter in the EOI group: LOS (MD: -2.509; 95% CI: -3.489, -1.529; I2 : 90.44%). For ENR (4 studies, n = 295), ENR (removed at POD0-2 vs. 5-8 days) was not associated with differences in risk of: anastomotic leak (RR: 1.11; 95% CI 0.336, 3.697; I2 : 25.75%) and pneumonia group (RR: 1.11; 95% CI: 0.336, 3.697; I2 : 25.75%), mortality (RR: 0.87; 95% CI: 0.328, 2.308; I2 : 0%)or LOS (MD: 1.618; 95% CI: -1.447, 4.683; I2 : 73.03%). CONCLUSIONS: Our analysis showed that EOI as well as ENR post-esophagectomy do not significantly increase the risk of anastomotic leak, pneumonia, and mortality. The LOS was significantly shorter in the EOI group, and there was no significant difference in the ENR group. A paucity of RCTs has evaluated this question, highlighting the need for further high-quality evidence to address these vital aspects to post-esophagectomy care. SYSTEMATIC REVIEW REGISTRATION: CRD42019138600.

The effect of immediate breast reconstruction on adjuvant therapy delay, locoregional recurrence, and disease-free survival.

BACKGROUND: An important risk inherent to both alloplastic and autologous immediate breast reconstruction (IBR) is the higher incidence of postoperative complications and delays to adjuvant therapy. The main objective of this retrospective cohort study was to identify risk factors for locoregional recurrence after breast cancer mastectomy and IBR. METHODS: A 6-year retrospective study of breast cancer patients treated with mastectomy only (MO) or mastectomy and IBR (MIBR) was conducted from January 2013 to May 2019. The outcomes of interest included delay in adjuvant chemoradiotherapy, postoperative complications, and locoregional recurrence. Cox regression survival was used to estimate the risk of locoregional recurrence and time to adjuvant therapy. RESULTS: Of 1832 patients reviewed, 720 (38%) were included. The cohort consisted of 443 (62%) MO and 277 (38%) MIBR [140 (51%) direct-to-implant (MIBRi1), 96(35%) tissue expander to implant (MIBRi2), and 41(15%) autologous flap (MIBRf)]. MIBR had more delays to adjuvant therapy compared to MO [113 (70%) vs. 72 (80%) months, p = 0.022]. Kaplan-Meier analysis showed that MIBRi2 had significantly shorter DFS compared to MO [MIBRi2: 39.2 (15.6) vs MO: 41.7 (19.6) months, log-rank p-value = 0.01]. Cox regression indicated that MIBRi2 was associated with a 3.26-higher risk of locoregional recurrence compared to MO [HR: 3.26; 95% CI: 1.56, 9.24]. CONCLUSIONS: Cox regression showed MIBRi2 was significantly associated with increased risk of locoregional recurrence compared to MO. Neither delays nor postoperative complications were identified as significant risk factors for locoregional recurrence risk.

Interventions to prevent anastomotic leak after esophageal surgery: a systematic review and meta-analysis.

BACKGROUND: Anastomotic leakage (AL) is a common and serious complication following esophagectomy. We aimed to provide an up-to-date review and critical appraisal of the efficacy and safety of all previous interventions aiming to reduce AL risk. METHODS: We searched MEDLINE and Embase from 1946 to January 2019 for randomized controlled trials (RCTs) evaluating interventions to minimize esophagogastric AL. Pooled risk ratios (RR) for AL were obtained using a random effects model. RESULTS: Two reviewers screened 441 abstracts and identified 17 RCTs eligible for inclusion; 11 studies were meta-analyzed. Omentoplasty significantly reduced the risk of AL by 78% [RR: 0.22; 95% CI: 0.10, 0.50] compared to conventional anastomosis (3 studies, n = 611 patients). Early removal of NG tube significantly reduced the risk of AL by 62% [RR: 0.38; 95% CI: 0.02, 0.65] compared to prolonged NG tube removal (2 studies, n = 293 patients); Stapled anastomosis did not significantly reduce the risk of AL [RR: 0.92; 95% CI: 0.45, 1.87] compared to hand-sewn anastomosis (6 studies, n = 1454 patients). The quality of evidence was high for omentoplasty (vs. conventional anastomosis), moderate for early NG tube removal (vs. prolonged NG tube removal), and very low for stapled anastomosis (vs. hand-sewn anastomosis). CONCLUSIONS: This is the first meta-analysis to summarize the graded quality of evidence for all RCT interventions designed to reduce the risk of AL following esophagectomy. Our findings demonstrated that omentoplasty significantly reduced the risk of AL with a high quality of evidence. Although early NG tube removal significantly reduced AL risk, there is a need for further research to strengthen the quality of evidence for this finding. Evidence profiles presented in our review may help inform the development of future clinical practice recommendations. Systematic review registration: CRD42019127181.

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis.

Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize the efficacy and safety of CAR-T cell therapy in patients with relapsed or refractory hematologic or solid malignancies. MEDLINE, Embase, and the Cochrane Register of Controlled Trials (inception - November 21, 2017). Interventional studies investigating CAR-T cell therapy in patients with malignancies were included. Our primary outcome of interest was complete response (defined as the absence of detectable cancer). Two independent reviewers extracted relevant data, assessed risk of bias, and graded the quality of evidence using established methods. A total of 42 hematological malignancy studies and 18 solid tumor studies met were included (913 participants). Of 486 evaluable hematologic patients, 54.4% [95% CI, 42.5%-65.9%] experienced complete response in 27 CD19 CAR-T cell therapy studies. Of 65 evaluable hematologic patients, 24.4% [95% CI, 9.4%-50.3%] experienced complete response in seven non-CD19 CAR-T cell therapy studies. Cytokine release syndrome was experienced by 55.3% [95% CI, 40.3%-69.4%] of patients and neurotoxicity 37.2% [95% CI, 28.6%-46.8%] of patients with hematologic malignancies. Of 86 evaluable solid tumor patients, 4.1% [95% CI, 1.6%-10.6%] experienced complete response in eight CAR-T cell therapy studies. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. There was a strong signal for efficacy of CAR-T cell therapy in patients with CD19+ hematologic malignancies and no overall signal in solid tumor trials published to date. These results will help inform patients, physicians, and other stakeholders of the benefits and risks associated with CAR-T cell therapy.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis.

INTRODUCTION: Patients with relapsed or refractory malignancies have a poor prognosis. Immunotherapy with chimeric antigen receptor T (CAR-T) cells redirects a patient's immune cells against the tumour antigen. CAR-T cell therapy has demonstrated promise in treating patients with several haematological malignancies, including acute B-cell lymphoblastic leukaemia and B-cell lymphomas. CAR-T cell therapy for patients with other solid tumours is also being tested. Safety is an important consideration in CAR-T cell therapy given the potential for serious adverse events, including death. Previous reviews on CAR-T cell therapy have been limited in scope and methodology. Herein, we present a protocol for a systematic review to identify CAR-T cell interventional studies and examine the safety and efficacy of this therapy in patients with haematology malignancies and solid tumours. METHODS AND ANALYSIS: We will search MEDLINE, including In-Process and Epub Ahead of Print, EMBASE and the Cochrane Central Register of Controlled Trials from 1946 to 22 February 2017. Studies will be screened by title, abstract and full text independently and in duplicate. Studies that report administering CAR-T cells of any chimeric antigen receptor construct targeting antigens in patients with haematological malignancies and solid tumours will be eligible for inclusion. Outcomes to be extracted will include complete response rate (primary outcome), overall response rate, overall survival, relapse and adverse events. A meta-analysis will be performed to synthesise the prevalence of outcomes reported as proportions with 95% CIs. The potential for bias within included studies will be assessed using a modified Institute of Health Economics tool. Heterogeneity of effect sizes will be determined using the Cochrane I 2 statistic. ETHICS AND DISSEMINATION: The review findings will be submitted for peer-reviewed journal publication and presented at relevant conferences and scientific meetings to promote knowledge transfer. PROSPERO REGISTRATION NUMBER: CRD42017075331.

Impact of Adverse Events and Length of Stay on Patient Experience After Lung Cancer Resection.

BACKGROUND: Postoperative adverse events (AEs), prolonged length of stay (PLOS), and patient experience are common quality measures after thoracic surgical procedures. Our objective was to investigate the relationship of postoperative AEs on patient experience and hospital length of stay (LOS) after lung cancer resection. METHODS: AEs (using Thoracic Morbidity and Mortality system based on Clavien-Dindo schema) and LOS were prospectively collected for all patients undergoing lung cancer resection. A 21-item questionnaire, retrospectively asking about patient experience, was mailed to patients twice (October 2015 and January 2016). The impact of AEs on experience was investigated and stratified by hospital LOS, with PLOS defined as the 75th percentile. Univariate analysis used parametric (t test) and nonparametric (Mann-Whitney) tests according to test conditions. RESULTS: Of 288 patients who responded to the survey (70% response rate), 175 (61%) had no AEs, 113 (39%) had experienced at least one AE, and 52 (18%) had experienced PLOS. Lung cancer patients who experienced PLOS showed significantly decreased experience on several questionnaire items, including their impression of comprehensiveness of surgeons information provision during inpatient period (p = 0.008), inpatient recovery from operation (p = 0.001), quality of life 30 days after operation (p = 0.032), follow-up care, (p = 0.022), and satisfaction with outcome 1 year after operation during follow-up care (p = 0.022). The presence of postoperative AEs led only to reduced impression about inpatient recovery from the operation (p = 0.01). CONCLUSIONS: In this cohort, postoperative AEs were minimally associated with negative patient experience. However, patients who experienced PLOS demonstrated a marked reduction in experience after thoracic surgical procedures.